This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.This project aims to elucidate mechanisms of myocardial force generation and relaxation in mice through (a) the study of the cardio-depressive effects of inhalational anesthesia at the cellular and tissue levels; (b) the hemodynamic assessment of global mechanical function using invasive catheterization techniques in normal states and with the use of inotropic agents, that include calcium analogs or intracellular agonists; and (c) non-invasive characterization of the murine cardiac function (strain tensor imaging) using Magnetic Resonance Imaging (MRI). All such aims will contribute in part to the complete characterization of the mouse model as a potentially useful model (structure-function, metabolism, perfusion) for extrapolation of scientific conclusions to man, and will ultimately allow comparative analyses of functional genomics in the mouse heart. Collectively, this project aims to develop the technological platform that will allow detailed studies of the cardiovascular system at the molecular, cellular, tissue and organ levels, addressing fundamental questions of the role of genetic cues in human cardiovascular disease, establishing at the same time the scientific platform for the development of a state-of-the-art animal imaging facility in Cyprus. In addition to the scientific value, the value for health care delivery and disease management, such a project will stimulate mobility efforts between USA, Europe and Cyprus and help attract investigators for the pursuit of such work, enable access opportunities to expertise and resources, and establish training programs polarised towards the transfer of knowledge from the USA to Europe and Cyprus, improving the skills and knowledge of European researchers. In all cases novel and superior products to existing ones, new employment opportunities in the high-technology sector would also offer a direct service to society, scientifically and through improvements in the value of the health care delivery and quality of life.The technical research and broader mobility and societal goals will be pursued through this proposed project, within the context of the analysis of the cardiodepressive effects of anesthesia on the animal physiology and myocardial contraction and relaxation, the study of global mechanical function and material properties of tissue at normal states and after positive inotropic intervention of calcium analogs or agonists. Technically, the project is targeted to address its objectives through the proposed research work in the elucidation of mechanisms of cardiac function and the application of pharmacological inotropic agents, as well as the direct use of the developed techniques in the study of mice with transgenic changes. Also, due to its multidisciplinary nature in physiology, cellular signalling, transgenesis, tissue engineering and bioimaging, multidisciplinary research efforts will be stimulated in the respective areas for the development of tools and techniques to study function, to analyse cellular mechanisms that mediate cardiodepression,, and to identify and study critical genetic foci that lead to prominent cardiomyopathies and heart failure.
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